Human cells are under constant threat of damage from external and internal sources. Accumulated DNA damages lead to cell death and genome instability, which can cause cancer, neurodegenerative disease and ageing. How do cells respond and deal with DNA damages is a fundamental biological question, and it is still not fully understood. Maintaining the integrity of genetic information stored in DNA through various damage response and repair signalling pathways are critical for cellular function and cell survival. Proteins involved in these signalling pathways form a dynamic and complex interaction network. It is crucial to identify and understand the structural and functional mechanisms of these proteins not only as individuals, but more importantly as complexes. These form the objectives of our research.

We study DNA damages that can lead to double-strand breaks (DSBs) which are the most toxic damages in cells. We would like to understand how key DNA damage response proteins respond to these DNA damages especially during DNA replication. We use integrated approaches with focus on the structural determinations of these complexes using cryo-EM and X-ray crystallography. Together with various biochemical/biophysical methods, cellular studies, isolation of protein tools targeting protein-protein interface, we would like to work out the exact mechanisms of these pathways at a molecular level. More detail of our world leading facilities can be found in here.

We strongly believe that one of the core values of basic biomedical research is translation into tools and treatment to improve human health. Therefore, through our research, we would like to understand how these DNA damage response pathways go wrong in cancer cells compared with normal cells. This will enable us to identify suitable targets to develop small molecule compounds that modulate the DNA damage response and repair signaling for future drug discovery, medical applications and ultimately killing cancer cells specifically.